title: Choice of comparator in active control trials of new drugs.
abstract: BACKGROUND
  When choosing the active control group in a randomized trial, it is important to maintain standard treatment for the therapeutic indication for which a medicine is studied. This choice is relevant not only for demonstrating the efficacy and safety of a new drug, but also for assessing its place in therapy in comparison with existing medicines. Comparative information is important for decisions on prescribing and reimbursement. However, choosing the most suitable comparator is difficult when recommendations on drugs of first choice vary depending on clinical settings and times.
  
  
  OBJECTIVE
  To evaluate the choice of comparator in premarketing randomized active control trials (RaCTs) in comparison with recommendations for standard treatment.
  
  
  METHODS
  We evaluated drugs that were authorized for use in the European Union market between 1999 and 2005. Information on active comparators in RaCTs was extracted from the European Public Assessment Reports and information on recommendations regarding standard treatment was retrieved from the annual editions of the Dutch reference book on pharmacotherapy. Data on prescribing and indications at the time of authorization and 3 years before authorization were included. The comparator was considered to be in line with standard treatment if there was a similarity in both active substance or therapeutic class and the dosage.
  
  
  RESULTS
  For 58 new medications identified, treatment in the active control group was in line with the recommended standard treatment in 108 of 153 (71%) RaCTs at the time of the drug's authorization; 47 (81%) of the new drugs had been compared with the recommended standard treatment in at least one trial. When dissimilarities occurred, none of the comparators had been recommended as standard treatment 3 years earlier (the supposed time of defining the trials' protocol).
  
  
  CONCLUSIONS
  Most comparators in the premarketing RaCTs of new medicines were in line with the recommended standard treatment at the moment of marketing authorization. In view of this similarity, most of these trials are also fit for postmarketing decision-making on prescribing and on inclusion in clinical guidelines and reimbursement systems.
authors.affiliation: Health Care Insurance Board, Diemen, Netherlands.
authors.forename: Johan C F
authors.initials: JC
authors.lastname: van Luijn
authors.forename: Arie C
authors.initials: AC
authors.lastname: van Loenen
authors.forename: Frank W J
authors.initials: FW
authors.lastname: Gribnau
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
mesh_terms: D035061:Control Groups; D017277:Drug Approval / Q000331:legislation & jurisprudence; D005062:European Union; D006801:Humans; D004364:Pharmaceutical Preparations; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations